SIK3 Recombinant Rabbit mAb (S-4947-62)

SIK3 (salt-inducible kinase 3) is a member of the AMPK protein kinase family, encoded by the SIK3 gene, and is widely expressed in human tissues, with the highest abundance found in the brain. Its protein structure comprises an N-terminal kinase domain, a ubiquitin-associated domain, and a C-terminal regulatory region, and its function is activated by phosphorylation via the upstream kinase LKB1, while being inhibited by PKA-mediated phosphorylation. SIK3 participates in regulating various physiological processes, and is most widely known for its core role as a "sleepiness gene" in sleep-wake and circadian rhythm regulation—gain-of-function mutations can significantly increase sleep need, while knockout disrupts circadian rhythms. In skeletal development, SIK3 is required for normal bone development by phosphorylating HDAC4 to anchor it in the cytoplasm, thereby relieving the inhibition of MEF2C, a key transcription factor for chondrocyte hypertrophy, and its loss of function can lead to Krakow-type spondyloepimetaphyseal dysplasia. In addition, SIK3 predominantly plays a tumor-promoting role in tumor biology, being highly expressed in breast cancer and ovarian cancer, where it drives cancer cell proliferation by promoting G1/S phase transition, and is associated with tumor antigenicity in ovarian cancer. In terms of metabolism and immunity, SIK3 is also involved in lipid metabolism regulation, suppression of macrophage inflammatory responses, and maintenance of endoplasmic reticulum homeostasis.